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Expression profiles of 76 necroptosis-related genes were analyzed in TCGA-STAD patients, generating a six-gene risk score model using LASSO regression and validating it in an independent cohort. 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Necroptosis Related Genes Predict Prognosis and Therapeutic Potential in Gastric Cancer. Biomolecules 2023, 13, 101. [https://doi.org/10.3390/](https://doi.org/10.3390/)[ ](https://doi.org/10.3390/)biom13010101  \nAcademic Editor: C²dric R²b²  \nReceived: 16 November 2022  \nRevised: 22 December 2022  \nAccepted: 2 January 2023  \nPublished: 4 January 2023  \nCopyright: © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://](https://)[ ](https://)[creativecommons.org/licenses/by/](creativecommons.org/licenses/by/)[ ](creativecommons.org/licenses/by/)[4.0/](4.0/)) .  \n1 The Comprehensive Cancer Centre of Nanjing Drum Tower Hospital, Clinical College of Nanjing Medical University, Nanjing 210009, China  \n2 Department of Pathology, Drum Tower Hospital, Medical School of Nanjing University, Nanjing 210009, China  \n3 The Comprehensive Cancer Centre of Nanjing Drum Tower Hospital, Clinical College of Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210009, China  \n4 Department of Oncology, The Second People's Hospital of Huai'an, Huai'an 223022, China  \n5 The Comprehensive Cancer Centre of Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing 210009, China  \n6 The Comprehensive Cancer Centre of Nanjing Drum Tower Hospital, Clinical College of Xuzhou Medical University, Nanjing 210009, China  \n* [Correspondence: baoruiliu@nju.edu.cn](Correspondence: baoruiliu@nju.edu.cn); Tel.: +86-25-83107081 † These authors contributed equally to this work and share first authorship.  \nAbstract: The clinical significance of necroptosis in gastric cancer (GC) has yet to be fully elucidated. The purpose of our study was to identify a necroptosis-relevant gene and to establish a prediction model to estimate the prognosis and therapeutic potential in GC. Here, we explored the expression profile of 76 necroptosis-related genes in TCGA-STAD patients. A six-gene risk score prediction model was established via regression analysis of the least absolute shrinkage and selection operator (LASSO) and validated in a separate cohort. Patients were separated into low-or high-risk groups according to the median risk score. We then compared and analyzed the biological process characteristics of two risk groups. Additionally, cell-to-cell communications and metabolic activity were analyzed in a single-cell solution. The in vitro experiments were conducted to explore the biological functions and drug sensitivity of necroptosis-related genes in gastric cancer. Our results identified that compared with the low-risk group, the high-risk group was associated with a higher clinical stage or grade and a worse prognosis. In addition, the low-risk group had higher levels of immunity and immune cell infiltration. Necroptosis was triggered by the TNF pathway in myeloid cells and the glycolysis pathway was altered. Necroptosis-related genes modulated the cell function, including proliferation and migration in vitro. Furthermore, the potential drugs' sensitivity was higher in the low-risk subgroup. These findings could facilitate a better understanding and improve the treatment potential and prognosis of GC patients.  \nKeywords: gastric cancer; necroptosis; immune cell infiltration; immune microenvironment; glycolysis; drug response  \n1. Introduction  \nGastric cancer (GC) is a complex and heterogeneous disease and is the third most common cause of cancer death worldwide [1] . Although chemotherapy and targeted therapy based on novel molecular characteristics have prov","cbCaijb3bszVGG0S","https://ap.wps.com/l/cbCaijb3bszVGG0S","pdf",6723397,"English","# Introduction\n## Background: gastric cancer and cell death\n# Abstract and study purpose\n# Methods and model construction\n## Gene expression profiling and LASSO risk model\n## Validation cohort and risk stratification\n# Results and analyses\n## Prognosis and clinical stage association\n## Immune infiltration and immune microenvironment\n## Pathway mechanisms and biological processes\n## Cell-to-cell communication and metabolic activity\n# Experimental validation\n## In vitro functions and drug sensitivity\n# Conclusion","[{\"question\":\"What was the main goal of this study in gastric cancer?\",\"answer\":\"To identify necroptosis-relevant genes and establish a prediction model that estimates prognosis and therapeutic potential in gastric cancer.\"},{\"question\":\"How were patients classified in the prediction model?\",\"answer\":\"Patients were separated into low- and high-risk groups according to the median six-gene risk score.\"},{\"question\":\"What relationship did the study find between risk score and prognosis/clinical features?\",\"answer\":\"The high-risk group showed higher clinical stage or grade and a worse prognosis compared with the low-risk group, with differences also reflected in immune infiltration levels.\"}]","Necroptosis Related Genes Predict Prognosis and Therapeutic Potential in Gastric Cancer | PDF",1790248623]